Referenced in: none

Automatically associated channels: Kv1.3

Title: Potent Kv1.3 inhibitors from correolide-modification of the C18 position.

Authors: Jianming Bao, Shouwu Miao, Frank Kayser, Andrew J Kotliar, Robert K Baker, George A Doss, John P Felix, Randal M Bugianesi, Robert S Slaughter, Gregory J Kaczorowski, Maria L Garcia, Sookhee N Ha, Laurie Castonguay, Gloria C Koo, Kashmira Shah, Marty S Springer, Mary Jo Staruch, William H Parsons, Kathleen M Rupprecht

Journal, date & volume: Bioorg. Med. Chem. Lett., 2005 Jan 17 , 15, 447-51

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/15603971

Abstract
Kv1.3, the voltage-gated potassium channel in human T cells, represents a new target for treating immunosuppression and autoimmune diseases. Correolide (1), a pentacyclic natural product, is a potent and selective Kv1.3 channel blocker. Simplification of correolide via removal of its E-ring generates enone 4, whose modification produced a new series of tetracyclic Kv1.3 blockers. The structure-activity relationship for this class of compounds in two functional assays, Rb_Kv and human T cell proliferation, is presented herein. The most potent analog 43 is 15-fold more potent than correolide as inhibitor of human T cell proliferation.